condition found tbRes List
RES, Resveratrol: Click to Expand ⟱
Features: polyphenol
Found in red grapes and products made with grapes.
Resveratrol is a polyphenol compound found in various plant species, including grapes, berries, and peanuts.
• Anti-inflammatory effects, Antioxidant effects:
- Antiplatelet aggregation for stroke prevention
- BioAvialability use piperine
- some sources may use Japanese knotweed roots (Reynoutria Japonica - root) as source which might contain Emodin (laxative)
-known as Nrf2 activator, both in cancer and normal cells. Which raises controversity of use in ROS↑ therapies. Interestingly there are reports of NRF2↑ and ROS↑ in cancer cells. This raises the question of if it is a chemosensitizer. However other reports indicate NRF2 droping with Res, indicating it maybe a chemosenstizer.
- RES is also considered to be them most effective natural SIRT1↑ -activating compound (STACs).

However, in the presence of certain metals, such as copper or iron, resveratrol can undergo a process called Fenton reaction, which can lead to the generation of reactive oxygen species (ROS). The pro-oxidant effects of resveratrol are often observed at high concentrations, typically above 50-100 μM, and in the presence of certain metals or other pro-oxidant agents. In contrast, the antioxidant effects of resveratrol are typically observed at lower concentrations, typically below 10-20 μM.

Clinical trials have used doses ranging from 150 mg to 5 grams per day. Lower doses (< 1 g/day) are often well-tolerated, but higher doses might be necessary for therapeutic effects and can be associated with side effects.

-Note half-life 1-3 hrs?.
BioAv poor: min 5uM/L required for chemopreventive effects, but 25mg Oral only yeilds 20nM. co-administration of piperine
Pathways:
- usually induce ROS production in cancer cells, while reducing ROS in normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓,
- Lowers AntiOxidant defense in Cancer Cells: NRF2(typically increased), TrxR↓**, SOD↓, GSH↓ Catalase↓ HO1↓(wrong direction), GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, FAK↓, RhoA↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, EZH2↓, P53↑, HSP↓, Sp proteins↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, CK2↓, Hh↓, CD133↓, CD24↓, β-catenin↓, sox2↓, notch2↓, nestin↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells


cycE, Cyclin E: Click to Expand ⟱
Source:
Type:
Cyclin E regulates multiple downstream molecules, such as the retinoblastoma susceptibility gene (RB1) and the transcription factor E2F.
Cyclin E is a prognostic marker in breast cancer, its altered expression increased with the increasing stage and grade of the tumor.
Cyclin E is a regulatory protein that plays a critical role in the cell cycle, particularly in the transition from the G1 phase to the S phase. Its expression levels can significantly influence cancer progression and patient prognosis.

Cyclin E expression is frequently elevated in various cancers and is generally associated with poor prognosis. Its role in promoting cell cycle progression makes it a potential biomarker for tumor aggressiveness and patient outcomes.


Scientific Papers found: Click to Expand⟱
993- RES,    Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells
- in-vitro, CRC, Caco-2 - in-vivo, Nor, HCEC 1CT
TumCG↓,
Glycolysis↓,
PPP↓,
ATP↑, significant increase (20%) in ATP production
PDH↑, Resveratrol targets the pyruvate dehydrogenase (PDH) complex, a key mitochondrial gatekeeper of energy metabolism, leading to an enhanced PDH activity.
Ca+2↝, resveratrol is a potent modulator of many cellular Ca2+ signaling pathways. Ca2+ is a key mediator of the effect of resveratrol on the oxidative capacity of colon cancer cells.
TumCP↓,
lactateProd↓,
OCR↑, increase of oxygen consumption rate (OCR) both in normal colonic epithelial HCEC 1CT cells
ECAR↓, Following treatment with resveratrol (10 µM, 48 hr), the ECAR was unchanged in normal HCEC 1CT cells, whereas it was significantly reduced (31%) in HCEC 1CT RPA cells ****
*ECAR∅, Following treatment with resveratrol (10 µM, 48 hr), the ECAR was unchanged in normal HCEC 1CT cells
*other?, Resveratrol promotes a shift from respiration to glycolysis in cancer-like cells, but not in normal colonocytes
cycE↑, Resveratrol inhibited cell cycle progression by enhancing the levels of cyclin E and cyclin A
cycA1↑,
TumCCA↑,
cycD1↑, and by decreasing cyclin D1
OXPHOS↑, Taken together, these observations indicate that exposure to resveratrol leads to a metabolic reorientation from aerobic glycolysis toward OXPHOS.


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Results for Effect on Cancer/Diseased Cells:
ATP↑,1,   Ca+2↝,1,   cycA1↑,1,   cycD1↑,1,   cycE↑,1,   ECAR↓,1,   Glycolysis↓,1,   lactateProd↓,1,   OCR↑,1,   OXPHOS↑,1,   PDH↑,1,   PPP↓,1,   TumCCA↑,1,   TumCG↓,1,   TumCP↓,1,  
Total Targets: 15

Results for Effect on Normal Cells:
ECAR∅,1,   other?,1,  
Total Targets: 2

Scientific Paper Hit Count for: cycE, Cyclin E
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:141  Target#:378  State#:%  Dir#:%
wNotes=on sortOrder:rid,rpid

 

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